The experiments currently under way and proposed for the coming year seek to examine the mechanisms of diethylstilbestrol (DES) action on the developing fetus. Unlike many previous studies on this subject we administer the DES transplacentally, before or during the period of sexual differentiation. These parameters most nearly simulate the conditions of human fetal exposure to the drug. The object of our first experiment is to identify the specific sites of 3H-DES localization in the developing fetus on the day when transplacental DES treatment causes its teratogenic effects on the urogential system. Two groups of 15 day pregnant mice are treated with DES and histological alterations in various tissues are confirmed in offspring on day 23 p.p. Two additional groups are injected with 3H-DES on day 15 p.c. and fetuses are processed for diffusible autoradiography to correlate sites of 3H-DES localization with alterations in histology. A second set of experiments seeks to determine whether transplacental DES treatment results in altered ovarian hormone uptake in adult target tissues. Twenty-three day old offspring transplacentally treated with DES will be injected with 3H-estradiol or 3H-R5020 (Promegestone). Quantitative dry-autoradiography will compare hormone uptake in individual cell types of brain, pituitary and urogenital system of the DES-treated and untreated mice.